liposomal doxorubicin and interleukin-12 in treating patients with aids-related kaposi's sarcoma

Conditions: Sarcoma

Summary: rationale: drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill the tumor cells. combining chemotherapy with interleukin-12 may kill more tumor cells. purpose: phase ii trial to study the effectiveness of combining liposomal doxorubicin with interleukin-12 in treating patients who have aids-related kaposi's sarcoma.

objectives: * determine the overall response rate in patients with aids-associated kaposi's sarcoma (ks) treated with doxorubicin hcl liposome and interleukin-12. * determine the time to response and the number of complete responses in patients treated with this regimen. * determine the progression-free survival of patients treated with this regimen. * provide pilot information on the ability of interleukin-12 to maintain major responses induced with paclitaxel salvage therapy in patients with aggressive or life-threatening ks after treatment failure with doxorubicin hcl liposome and interleukin-12. * determine the effect of this regimen on cd4 counts and viral load in these patients. outline: patients receive doxorubicin hcl liposome (lipodox) iv over 30 minutes once every 3 weeks for a total of 6 doses. beginning concurrently with the initiation of lipodox, patients also receive interleukin-12 (il-12) subcutaneously twice weekly (at least 3 days apart) for up to 3 years. patients with refractory disease are transferred to the paclitaxel salvage therapy regimen comprising paclitaxel iv continuously on days 1-4 once every 3 weeks until a major response is achieved. beginning concurrently with the initiation of paclitaxel salvage therapy, patients also receive il-12 as above for up to 3 years. treatment continues in the absence of disease progression or unacceptable toxicity. patients achieving a complete response may discontinue il-12 administration. if necessary, il-12 treatment may resume at a later time. patients are followed at 4 weeks. projected accrual: a total of 24-36 patients will be accrued for this study within 2-4 years.

Eligibility criteria:
disease characteristics: * histologically confirmed kaposi's sarcoma (ks) * hiv positive * evaluable disease involving the skin and/or viscera * at least 5 lesions not previously treated with local therapy if restricted to the skin * pulmonary lesions evaluable by ct scan * gastrointestinal lesions evaluable by visualization or fiberoptic instrumentation * presence of at least one of the following indications for cytotoxic chemotherapy: * pulmonary involvement * visceral involvement * pain * edema * ulcerating lesions * decreased range of joint motion due to ks * multiple lesions not amenable to local therapy * lymphedema that impairs mobility or range of motion * significant psychological impact leading to social withdrawal * progressive disease within the past 3 weeks while receiving a stable regimen of highly active antiretroviral therapy for at least 4 weeks unless there is a need for urgent chemotherapy * prior participation on this study allowed, provided patient was removed from study due to non-pancreatic hyperamylasemia and the following are true: * no dose-limiting toxicity by clinical and laboratory assessment * pancreatic amylase portion normal by fractionated amylase * lipase normal * no symptoms referable to the pancreas patient characteristics: age: * 18 and over performance status: * karnofsky 30-100% life expectancy: * more than 2 months hematopoietic: * hemoglobin at least 9.0 g/dl * absolute neutrophil count at least 750/mm\^3 * platelet count at least 75,000/mm\^3 hepatic: * bilirubin no greater than 3.8 mg/dl with direct fraction no greater than 0.3 mg/dl and indirect fraction no greater than 3.5 mg/dl if due to protease inhibitor therapy * pt or aptt no greater than 120% of control unless due to lupus-type anticoagulant * ast no greater than 2.5 times upper limit of normal * no prior hepatic cirrhosis * no hepatic dysfunction renal: * creatinine no greater than 1.5 mg/dl * creatinine clearance at least 60 ml/min cardiovascular: * no congestive heart failure * ejection fraction at least 40% by muga or echocardiogram other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective barrier contraception during and for 2 months after study participation * no clinically significant autoimmune disease * no active, gross gastrointestinal bleeding or uncontrolled peptic ulcer disease * no prior inflammatory bowel disease * no other prior or concurrent malignancy except squamous cell carcinoma in situ of the cervix or anus, completely resected basal cell carcinoma, or malignancy in complete remission for at least 1 year from the time a response was first documented * no severe or life-threatening infection within the past 2 weeks * no abnormality that would be scored as grade 3 toxicity except lymphopenia or direct manifestations of ks * no known hypersensitivity to interleukin-12 (il-12) or other compounds known to cross-react with il-12 * no other medical condition that would preclude study entry prior concurrent therapy: biologic therapy: * more than 2 weeks since prior cytokines or colony-stimulating factors other than epoetin alfa, filgrastim (g-csf), or sargramostim (gm-csf) * no prior combination interleukin-12 and doxorubicin hcl liposome except for patients previously treated on this protocol who are being enrolled for paclitaxel salvage therapy * no concurrent immunomodulatory agents * no concurrent cytokines except epoetin alfa or g-csf chemotherapy: * see disease characteristics * see biologic therapy * at least 3 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) * more 6 months since prior suramin * no other concurrent cytotoxic chemotherapy endocrine therapy: * more than 2 months since prior systemic glucocorticoid steroids at doses sufficient to affect immune response (e.g., more than 20 mg of prednisone for more than 1 week) * concurrent replacement glucocorticoid therapy allowed * no other concurrent systemic glucocorticoid therapy radiotherapy: * not specified surgery: * not specified other: * concurrent antiretroviral therapy required * no other concurrent anti-ks therapy

Keywords: aids-related kaposi sarcoma recurrent kaposi sarcoma